rs11205387

Variant names:

• chr1-150510262-G-A
• rs11205387
• NM_004425.4:c.385+80G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-150510262-G-A
• chr1-150510262-G-C
• chr1-150510262-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004425.4(ECM1):​c.385+80G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,337,306 control chromosomes in the GnomAD database, including 52,586 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5217 hom., cov: 32)
  • Exomes 𝑓: 0.28 (47369 hom.)
• Consequence: ECM1 NM_004425.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.65
• Publications: 20 publications found

Genes affected

ECM1 (HGNC:3153): (extracellular matrix protein 1) This gene encodes a soluble protein that is involved in endochondral bone formation, angiogenesis, and tumor biology. It also interacts with a variety of extracellular and structural proteins, contributing to the maintenance of skin integrity and homeostasis. Mutations in this gene are associated with lipoid proteinosis disorder (also known as hyalinosis cutis et mucosae or Urbach-Wiethe disease) that is characterized by generalized thickening of skin, mucosae and certain viscera. Alternatively spliced transcript variants encoding distinct isoforms have been described for this gene. [provided by RefSeq, Feb 2011]

ECM1 Gene-Disease associations (from GenCC):

• lipoid proteinosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P, Orphanet

ENSG00000307101 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-150510262-G-A is Benign according to our data. Variant chr1-150510262-G-A is described in ClinVar as [Benign]. Clinvar id is 1258875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECM1	NM_004425.4	c.385+80G>A		intron_variant	Intron 5 of 9	ENST00000369047.9	NP_004416.2
ECM1	NM_001202858.2	c.466+80G>A		intron_variant	Intron 5 of 9		NP_001189787.1
ECM1	NM_022664.3	c.385+80G>A		intron_variant	Intron 5 of 8		NP_073155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECM1	ENST00000369047.9	c.385+80G>A		intron_variant	Intron 5 of 9	1	NM_004425.4	ENSP00000358043.4

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39143 AN: 152024 Hom.: 5209 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.279 AC: 331045 AN: 1185164 Hom.: 47369 Cov.: 18 AF XY: 0.281 AC XY: 169038 AN XY: 601824

African (AFR) AF: 0.184 AC: 5109 AN: 27828

American (AMR) AF: 0.332 AC: 14557 AN: 43818

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 9206 AN: 24308

East Asian (EAS) AF: 0.357 AC: 13721 AN: 38414

South Asian (SAS) AF: 0.278 AC: 22401 AN: 80672

European-Finnish (FIN) AF: 0.318 AC: 16582 AN: 52190

Middle Eastern (MID) AF: 0.282 AC: 1476 AN: 5234

European-Non Finnish (NFE) AF: 0.271 AC: 233526 AN: 861306

Other (OTH) AF: 0.281 AC: 14467 AN: 51394

GnomAD4 genome AF: 0.257 AC: 39173 AN: 152142 Hom.: 5217 Cov.: 32 AF XY: 0.260 AC XY: 19305 AN XY: 74372

African (AFR) AF: 0.190 AC: 7908 AN: 41512

American (AMR) AF: 0.288 AC: 4403 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1315 AN: 3470

East Asian (EAS) AF: 0.303 AC: 1570 AN: 5174

South Asian (SAS) AF: 0.273 AC: 1314 AN: 4822

European-Finnish (FIN) AF: 0.310 AC: 3282 AN: 10576

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18363 AN: 67996

Other (OTH) AF: 0.281 AC: 594 AN: 2112

Alfa AF: 0.271 Hom.: 8232

Bravo AF: 0.258

Asia WGS AF: 0.324 AC: 1128 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.61
DANN	Benign	0.67
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11205387; hg19: chr1-150482738; COSMIC: COSV60872532; COSMIC: COSV60872532;